OBJ - Cell Cycle

Question 1

Stages in the cell cycle

Answer 1

Interphase
G1 Phase - Growth (Prep for S - most variable)
S Phase - DNA Synthesis
G2 Phase - Growth phase (Prep for M)

Mitosis
M Phase - Mitosis

Question 2

G1 Phase

Answer 2

Cells grow in size and functional output

1) Begins with brand new daughter cells
→ Make mRNAs and proteins
→ Expand organelles
→ Make ATP

2) Some cells remain in G1 for an extended period = G0 phase

3) Prepare for S phase
Make materials required for DNA synthesis
= Enzymes, nucleotides, ATP

Question 3

G0 Phase

Answer 3

just functioning, not prepping for DNA synthesis/growing

Question 4

S Phase

Answer 4

1) Duplicate each chromosome once and only once

homologues - 1 from mom & 1 from dad
sister chromatids - 2 mom & 2 dad

2) DNA packaging must also be copied - epigenetics
- Shift from heterochromatin -> euchromatin

Question 5

G2

Answer 5

1) Cells grow in preparation for division - become BIG cell & recover from DNA synthesis (ATP)
→ Make mRNAs and proteins
→ Expand more organelles
→ Make ATP & recover from S phase

2) Prepare for M phase

Make materials required for cell division
• Tubulin (for spindle microtubules)
• Other mitotic spindle proteins
• ATP

Question 6

Mitosis

Answer 6

Cell division:
1) Sister chromatid (DNA) separation
= mitosis or karyokinesis
2) Cytoplasmic division 
= cytokinesis

Mitotic spindle is the machine that separates sister chromatids It’s made of
Microtubules that attach to sister chromatids & pull them to opposite parts of the cell

5 Subphases of Mitosis:

• Prophase
• Prometaphase
• Metaphase
• Anaphase
• Telophase
• Cytokinesis

Phases are defined by:
• changes to the mitotic spindle
• amount of chromatid separation

Question 7

Mitotic Spindle

Answer 7

Centrosome = 2 poles on opposite sides

Centrioles - form basal bodies & anchors of Centrosomes

Spindle Equator = where the sister chromatids line up

Kinetichores = where microtubules attach

2 types of microtubules:

1) Kinetichore microtubules
2) Astral microtubules = off of Centrosomes

Question 8

Prophase

Answer 8

The “Prep” phase

• DNA condenses to form compact chromatids
  euchromatin -> heterochromatin
• Centrosomes move to opposite sides of
  the nucleus
• Microtubules begin to organize into the
  spindle

Question 9

Prometaphase

Answer 9

**Defining event **
The nuclear envelope (membrane) disintegrates

Then Spindle microtubules can begin attaching to kinetochores on sister chromatids

Question 10

Metaphase

Answer 10

**Defining event **
Chromosomes are aligned at the spindle equator

Sister chromatids are attached to opposite
poles of the spindle

Question 11

Anaphase

Answer 11

Cohesins that hold sister chromatids together are destroyed

Sister chromatids are separated and move toward opposite poles by 2 mechanisms:
1) Kinetochore microtubules shorten
2) The spindle poles move further apart
from one another

Question 12

Telophase

Answer 12

Chromosomes are fully separated to
opposite poles

The nuclear envelope reforms

DNA decondenses

Question 13

Cytokinesis

Answer 13

Division of the cytoplasm and all of its contents

• Accomplished by progressive constriction and final scission of the plasma membrane
• Where Metaphase Plate/spindle equator = establishes the location of cytokinesis

**Spindle needs to be parallel to tissue layer so integrity & tissue organization of cells is very important

• Active membrane addition is required to accommodate the increase in surface area

A contractile ring composed of actin and myosin inside the cell that pulls the plasma membrane inward as it constricts

Question 14

Cohesins

Answer 14

where sister chromatids are attached

“molecular glue” from lecture

Question 15

Mitogen

Answer 15

Signaling factors that tell the cell to divide that initiate signal transduction cascade

Environmental stimuli are most common mitogens

i.e. EPO, antigens, cytokines

Question 16

Cyclins

Answer 16

Proteins expressed at certain stages that direct certain events at that stage

ALWAYS work in pairs with CDK
CDK = cyclin dependent kinases

Turn on specific phase’s machinery through substrate phosphorylation
-specific to each stage

Cyclins Are Synthesized and Degraded During the Cell Cycle

• Synthesis is up-regulated of Cyclin
• Degraded by tagged by ubiquitin & then proteasome degrades cyclin, but leaves CDK

Question 17

Checkpoints in MItosis

Answer 17

CHECKPOINTS
- Pauses/Checkpoints Ensure that Problems Are Not Propagated

G1 Checkpoint (G1/S)
 - Have I  received mitogenic signal? Favorable environment? DNA damaged?

S Checkpoint
- DNA - is it ALL replicated? Any damaged?

Metaphase/Anaphase Checkpoint
- Sister chromatids attached to spindle pole

Good to go -> continues
Not -> Pauses & tries to fix -> can’t fix = apoptosis

Cdk Inhibitor (CKI) Proteins are important regulators of the checkpoints
Proteins turned on when checkpoint not met
Turn off CDK complex, pausing cycle

Metaphase to Anaphase Transition:
1. GO signal activates the Anaphase Promoting Complex/Cyclosome (APC/C), a ubiquitin ligase

2. APC/C targets cohesins for destruction, which allows sister chromatids to be separated
3. APC/C also ubiquitylates cyclins, which targets them for destruction and triggers the completion of mitosis and cytokinesis

Question 18

Chemotherapeutics

Answer 18

Microtubule Poisons
Attack microtubule assembly

Herceptin
G1 activation is inhibited and prevents over-proliferation